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Sitagliptin for Hyperglycemia in Patients With T2DM Undergoing Cardiac Surgery (SITA-CABGDM)

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ClinicalTrials.gov Identifier: NCT02556918
Recruitment Status : Completed
First Posted : September 22, 2015
Last Update Posted : December 19, 2018
Sponsor:
Information provided by (Responsible Party):
Guillermo Umpierrez, MD, Emory University

Brief Summary:
The purpose of this study is to determine whether treatment with sitagliptin reduces the frequency and severity of high blood sugar (hyperglycemia) after cardiac surgery and to determine whether treatment with sitagliptin is effective in maintaining blood sugar control in patients with type 2 diabetes (T2D).

Condition or disease Intervention/treatment Phase
Hyperglycemia Drug: Sitagliptin Drug: Placebo Drug: Regular Human Insulin Drug: Insulin glargine Drug: Supplemental insulin (Insulin lispro) Drug: Supplemental insulin (Insulin aspart) Phase 4

Detailed Description:
The purpose of this study is to determine whether treatment with sitagliptin reduces the frequency and severity of high blood sugar (hyperglycemia) and the need for continuous intravenous insulin infusion (CII) in the intensive care unit (ICU) in patients with type 2 diabetes (T2D) undergoing coronary artery bypass graft (CABG) surgery. In addition, the study seeks to determine whether treatment with sitagliptin is effective in maintaining glycemic control and in preventing the need for subcutaneous (SC) insulin therapy in patients with T2D during the transition from intensive care unit (ICU) to regular floor in cardiac surgery patients with T2D.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 202 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Prevention
Official Title: Sitagliptin for the Prevention and Treatment of Hyperglycemia in Patients With Type 2 Diabetes Undergoing Cardiac Surgery
Study Start Date : January 2016
Actual Primary Completion Date : November 6, 2018
Actual Study Completion Date : November 6, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Sitagliptin

Subjects undergoing cardiac surgery with type 2 diabetes (T2D) will be randomized to receive one tablet of sitagliptin once a day.Subjects with stress hyperglycemia (defined as a blood glucose (BG) greater than 180 mg/dL) in the intensive care unit (ICU) will continue to receive sitagliptin and will be started on continuous intravenous insulin (Regular Human Insulin) adjusted to achieve and maintain a BG target between 110 - 180 mg/dL following standard hospital protocol. Additionally, once moved to the regular floors and out of ICU, the subjects can receive insulin glargine, insulin lispro, and/or insulin aspart depending on the blood glucose level.

Interventions:

Drug: Sitagliptin Drug: Regular Human Insulin Drug: Insulin glargine Drug: Supplemental insulin (Insulin lispro) Drug: Supplemental insulin (Insulin aspart)

Drug: Sitagliptin
Subjects will take one pill daily starting one day prior to surgery until discharge from the hospital. Sitagliptin will be dispensed orally at 100 mg/day for patients with a glomeruler filtration rate (GFR) greater than or equal to 50. Patients with a GFR between 30-49 will receive 50 mg/day.
Other Name: Januvia

Drug: Regular Human Insulin
Continuous intravenous insulin given to intensive care unit (ICU) patients with a blood glucose (BG) greater than 180 mg/DL and will be started on Regular Human Insulin adjusted to achieve and maintain a BG target between 110 - 180 mg/dL following standard hospital protocol.Intravenous insulin infusion will be continued until the patient is able to eat and/or is transferred to non-ICU service. In previous studies, average length of insulin infusion in patients with stress hyperglycemia was 16.9±19 hours and the amount of IV insulin requirement was 18.6±24.3 U/day.
Other Names:
  • Novolin-R
  • Humulin-R

Drug: Insulin glargine

Patients that required continuous insulin infusion (CII) at a rate >1U/h will be transitioned to basal insulin (glargine/detemir). Calculate total daily dose (TDD) of insulin from the average CII rate during the last four hours of infusion (example, if the average rate is 2 U/hr., the TDD is 48 U/day) Give 50% of calculated dose as basal (glargine/detemir) insulin every day. Basal insulin will be given approx. 4 hours before discontinuation of CII.

The total daily insulin dose will be adjusted as follow:

Fasting and pre-meal BG between 100-180 mg/dl without hypoglycemia the previous day: no change Fasting and pre-meal BG between >180-240 mg/dl: increase basal dose by 10% every day Fasting and pre-meal BG >241 mg/dl: increase basal dose by 20% every day Fasting and pre-meal BG <100 mg/dl: stop basal

Other Name: Lantus

Drug: Supplemental insulin (Insulin lispro)

Insulin lispro will be administered before meals in addition to scheduled insulin dose following the supplemental insulin scale protocol. At bedtime, half of supplemental sliding scale insulin starting at blood glucose (BG) greater than 240 mg/dL will be given. For the subjects receiving supplemental insulin lispro with BG levels greater than 180 mg/dL, then supplemental insulin scale is as follows:

  • BG between 181-220 mg/dL; 2-4 units of insulin lispro
  • BG between 221-260 mg/dL; 3-5 units of insulin lispro
  • BG between 261-300 mg/dL; 4-6 units of insulin lispro
  • BG between 301-350 mg/dL; 5-7 units of insulin lispro
  • BG between 351-400 mg/dL; 6-8 units of insulin lispro
  • BG greater than 400 mg/dL; 7-9 units of insulin lispro
Other Name: Humalog

Drug: Supplemental insulin (Insulin aspart)

Insulin aspart will be administered before meals in addition to scheduled insulin dose following the supplemental insulin scale protocol. At bedtime, half of supplemental sliding scale insulin starting at blood glucose (BG) greater than 240 mg/dL will be given. For the subjects receiving supplemental insulin aspart with BG levels greater than 180 mg/dL, then supplemental insulin scale is as follows:

  • BG between 181-220 mg/dL; 2-4 units of insulin aspart
  • BG between 221-260 mg/dL; 3-5 units of insulin aspart
  • BG between 261-300 mg/dL; 4-6 units of insulin aspart
  • BG between 301-350 mg/dL; 5-7 units of insulin aspart
  • BG between 351-400 mg/dL; 6-8 units of insulin aspart
  • BG greater than 400 mg/dL; 7-9 units of insulin aspart
Other Name: Novolog

Placebo Comparator: Placebo

Subjects undergoing cardiac surgery with type 2 diabetes will be randomized to receive one tablet of placebo once a day.Subjects with stress hyperglycemia (defined as a blood glucose (BG) greater than 180 mg/dL) in the intensive care unit (ICU) will continue to receive a placebo and will be started on continuous intravenous insulin (Regular Human Insulin) adjusted to achieve and maintain a BG target between 110 - 180 mg/dL following standard hospital protocol. Additionally, once moved to the regular floors and out of ICU, the subjects can receive insulin glargine, insulin lispro, and/or insulin aspart depending on the blood glucose level.

Interventions:

Drug: Placebo Drug: Regular Human Insulin Drug: Insulin glargine Drug: Supplemental insulin (Insulin lispro) Drug: Supplemental insulin (Insulin aspart)

Drug: Placebo
One pill daily starting one day prior to surgery until discharge from the hospital.

Drug: Regular Human Insulin
Continuous intravenous insulin given to intensive care unit (ICU) patients with a blood glucose (BG) greater than 180 mg/DL and will be started on Regular Human Insulin adjusted to achieve and maintain a BG target between 110 - 180 mg/dL following standard hospital protocol.Intravenous insulin infusion will be continued until the patient is able to eat and/or is transferred to non-ICU service. In previous studies, average length of insulin infusion in patients with stress hyperglycemia was 16.9±19 hours and the amount of IV insulin requirement was 18.6±24.3 U/day.
Other Names:
  • Novolin-R
  • Humulin-R

Drug: Insulin glargine

Patients that required continuous insulin infusion (CII) at a rate >1U/h will be transitioned to basal insulin (glargine/detemir). Calculate total daily dose (TDD) of insulin from the average CII rate during the last four hours of infusion (example, if the average rate is 2 U/hr., the TDD is 48 U/day) Give 50% of calculated dose as basal (glargine/detemir) insulin every day. Basal insulin will be given approx. 4 hours before discontinuation of CII.

The total daily insulin dose will be adjusted as follow:

Fasting and pre-meal BG between 100-180 mg/dl without hypoglycemia the previous day: no change Fasting and pre-meal BG between >180-240 mg/dl: increase basal dose by 10% every day Fasting and pre-meal BG >241 mg/dl: increase basal dose by 20% every day Fasting and pre-meal BG <100 mg/dl: stop basal

Other Name: Lantus

Drug: Supplemental insulin (Insulin lispro)

Insulin lispro will be administered before meals in addition to scheduled insulin dose following the supplemental insulin scale protocol. At bedtime, half of supplemental sliding scale insulin starting at blood glucose (BG) greater than 240 mg/dL will be given. For the subjects receiving supplemental insulin lispro with BG levels greater than 180 mg/dL, then supplemental insulin scale is as follows:

  • BG between 181-220 mg/dL; 2-4 units of insulin lispro
  • BG between 221-260 mg/dL; 3-5 units of insulin lispro
  • BG between 261-300 mg/dL; 4-6 units of insulin lispro
  • BG between 301-350 mg/dL; 5-7 units of insulin lispro
  • BG between 351-400 mg/dL; 6-8 units of insulin lispro
  • BG greater than 400 mg/dL; 7-9 units of insulin lispro
Other Name: Humalog

Drug: Supplemental insulin (Insulin aspart)

Insulin aspart will be administered before meals in addition to scheduled insulin dose following the supplemental insulin scale protocol. At bedtime, half of supplemental sliding scale insulin starting at blood glucose (BG) greater than 240 mg/dL will be given. For the subjects receiving supplemental insulin aspart with BG levels greater than 180 mg/dL, then supplemental insulin scale is as follows:

  • BG between 181-220 mg/dL; 2-4 units of insulin aspart
  • BG between 221-260 mg/dL; 3-5 units of insulin aspart
  • BG between 261-300 mg/dL; 4-6 units of insulin aspart
  • BG between 301-350 mg/dL; 5-7 units of insulin aspart
  • BG between 351-400 mg/dL; 6-8 units of insulin aspart
  • BG greater than 400 mg/dL; 7-9 units of insulin aspart
Other Name: Novolog




Primary Outcome Measures :
  1. Frequency of hyperglycemia in the intensive care unit (ICU) [ Time Frame: 2 days (average time of discharge from ICU) ]
    The percent of patients with blood glucose (BG) levels greater than 160 mg/dl

  2. Number of patients with persistent hyperglycemia [ Time Frame: 10 days (average time of discharge from the hospital) ]
    Number of patients with two consecutive fasting and/or pre-meal blood glucose (BG) greater than 180 mg/dl, or with average daily BG greater than 80 mg/dl who require rescue therapy with subcutaneous (SC) insulin after discontinuation of continuous intravenous insulin infusion (CII).


Secondary Outcome Measures :
  1. Rate of continuous intravenous insulin infusion (CII) for treatment of hyperglycemia [ Time Frame: 2 days (average time of discharge from ICU) ]
    Number of patients requiring CII to achieve a blood glucose level (BG) target between 150-200 mg/dl.

  2. Mean blood glucose (BG) concentration in the intensive care unit (ICU) [ Time Frame: 2 days (average time of discharge from ICU) ]
    Mean BG concentration of ICU patients during recovery period.

  3. Mean insulin dose per hour during intensive care unit (ICU) (ICU) recovery [ Time Frame: 2 days (average time of discharge from ICU) ]
    Mean insulin infusion dose per hour (unit/hour) of ICU patients during recovery period.

  4. Mean insulin dose per day during intensive care unit (ICU) recovery [ Time Frame: 2 days (average time of discharge from ICU) ]
    Mean insulin infusion dose per day of ICU patients during recovery period.

  5. Duration of continuous intravenous insulin infusion (CII) [ Time Frame: 2 days (average time of discharge from ICU) ]
    Total hours of continuous intravenous insulin infusion (CII)

  6. Number of patients requiring subcutaneous (SC) insulin after discontinuation of continuous intravenous insulin infusion (CII) [ Time Frame: 10 days (average time of discharge from the hospital) ]
    Total number of patients requiring subcutaneous (SC) insulin after discontinuation of continuous intravenous insulin infusion (CII)

  7. Days of subcutaneous (SC) insulin after discontinuation of continuous intravenous insulin infusion (CII) [ Time Frame: 10 days (average time of discharge from the hospital) ]
    Total number of days patients requiring SC insulin after discontinuation of CII

  8. Mean non-intensive care unit (ICU) blood glucose (BG) concentration [ Time Frame: 10 days (average time of discharge from the hospital) ]
    Mean BG concentration of non-ICU patients during recovery period.

  9. Amount of subcutaneous (SC) insulin taken in intensive care unit (ICU) [ Time Frame: 2 days (average time of discharge from ICU) ]
    Total amount of SC insulin taken by ICU patients during recovery period.

  10. Amount of subcutaneous (SC) insulin taken in non-intensive care unit (ICU) [ Time Frame: 10 days (average time of discharge from the hospital) ]
    Total amount of SC insulin taken by non-intensive care unit (ICU) patients during recovery period.

  11. Rate of hyperglycemic events in intensive care unit (ICU) [ Time Frame: 2 days (average time of discharge from ICU) ]
    Number of hyperglycemic events (blood glucose greater than or equal to 200 mg/dL) in ICU patients during recovery period.

  12. Rate of hyperglycemic events in non-intensive care unit (ICU) [ Time Frame: 10 days (average time of discharge from the hospital) ]
    Number of hyperglycemic events (blood glucose greater than or equal to 200 mg/dL) in non-ICU patients recovery period.

  13. Rate of hypoglycemic events in intensive care unit (ICU) [ Time Frame: 2 days (average time of discharge from ICU) ]
    Number of hypoglycemic events (blood glucose less than 70 mg/dL) in patients in intensive care unit (ICU).

  14. Rate of hypoglycemic events in non-intensive care unit (ICU) [ Time Frame: 10 days (average time of discharge from the hospital) ]
    Number of hypoglycemic events (blood glucose less than 70 mg/dL) in patients in non-intensive care unit (ICU).

  15. Rate of severe hypoglycemic events in intensive care unit (ICU) [ Time Frame: 2 days (average time of discharge from ICU) ]
    Number of severe hypoglycemia (blood glucose less than 40 mg/dL) in patients in intensive care unit (ICU).

  16. Rate of severe hypoglycemic events in non-intensive care unit (ICU) [ Time Frame: 10 days (average time of discharge from the hospital) ]
    Number of hypoglycemic events (blood glucose less than 40 mg/dL) in patients in non-intensive care unit (ICU).

  17. Composite of perioperative complications [ Time Frame: 10 days (average time of discharge from the hospital) ]
    Number of perioperative complications including hospital mortality,sternal wound infection, bacteremia, pneumonia, acute renal failure, and acute mycordial infarction.

  18. Duration of ventilary support [ Time Frame: 10 days (average time of discharge from the hospital) ]
    Total number of hours patients required to be on ventilary support.

  19. Length of intensive care unit (ICU) stay [ Time Frame: 2 days (average time of discharge from ICU) ]
    Total number of days spent in ICU

  20. Length of non-intensive care unit (ICU) hospital stay [ Time Frame: 10 days (average time of discharge from the hospital) ]
    Total number of days spent in hospital

  21. Number of intensive care unit (ICU) readmission [ Time Frame: 10 days (average time of discharge from the hospital) ]
    Number of re-admissions to intensive care unit during the same hospital course.

  22. Rate of cerebrovascular events [ Time Frame: 10 days (average time of discharge from the hospital) ]
    Number of cerebrovascular events including permanent stroke and reversible ischemic neurologic deficit

  23. Hospital readmission rate [ Time Frame: 30 days ]
    Number of subjects readmitted to the hospital within 30 days (all-cause).

  24. Emergency room visit rate [ Time Frame: 30 days ]
    Number of subjects returning to the ER within 30 days (all-cause).



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The ability to provide informed consent
  • Ages 18 to 80 years old
  • Male or female
  • Scheduled to undergo cardiac surgery
  • Type 2 Diabetes treated with diet, oral agents,

Exclusion Criteria:

  • Severely impaired kidney function (glomeruler filtration rate (GFR ) less than 30 ml/min)
  • Clinically significant liver failure
  • Imminent risk of death (brain death or cardiac standstill)
  • Gastrointestinal obstruction or adynamic ileus
  • Expected to require gastrointestinal suction
  • Clinically relevant pancreatic or gallbladder disease
  • Using oral or injectable corticosteroid
  • Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study
  • Female subjects are pregnant or breast feeding at time of enrollment into the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02556918


Locations
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United States, Georgia
Grady Health System
Atlanta, Georgia, United States, 30303
Emory Univeristy Hospital Midtown
Atlanta, Georgia, United States, 30308
Emory University Hospital
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
Investigators
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Principal Investigator: Guillermo Umpierrez, MD Emory University

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Responsible Party: Guillermo Umpierrez, MD, Professor, Emory University
ClinicalTrials.gov Identifier: NCT02556918     History of Changes
Other Study ID Numbers: IRB00082180
First Posted: September 22, 2015    Key Record Dates
Last Update Posted: December 19, 2018
Last Verified: December 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Guillermo Umpierrez, MD, Emory University:
Coronary artery bypass graft surgery (CABG)
Type 2 Diabetes
Additional relevant MeSH terms:
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Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Insulin
Insulin, Globin Zinc
Sitagliptin Phosphate
Insulin Glargine
Insulin Aspart
Insulin, Long-Acting
Insulin degludec, insulin aspart drug combination
Insulin Lispro
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action